High affinity humanized anti-TAG-72 monoclonal antibodies

Abstract

Novel humanized monoclonal antibodies, humanized antibody fragments, and derivatives thereof which specifically bind TAG-72 are provided as well as methods for their manufacture. These humanized antibodies are useful in the treatment of cancers which express TAG-72 as well as for diagnostic purposes, e.g., for in vivo imaging of tumors or cancer cells which express TAG-72.

What is claimed is:  
     
       1. A method for in vivo treatment of a mammal having a TAG-72-expressing cancer comprising a step of administering to the mammal a therapeutically effective amount of a composition suitable for the treatment of cancer, said composition containing either: 
       A) a therapeutically effective amount of a humanized antibody directly or indirectly attached to an effector moiety having therapeutic activity, said humanized antibody having binding specificity to TAG-72 and said humanized antibody comprising:  
       1) at least one NEWM-grafted humanized heavy chain variable region (VH) having the amino acid sequence of any one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6; and  
       2) at least one REI-grafted humanized light chain variable region (VL) having the amino acid sequence of SEQ ID NO:9; or  
       B) a therapeutically effective amount of a humanized antibody fragment directly or indirectly attached to an effector moiety having therapeutic activity, said fragment being a fragment of the humanized antibody of Part A) and said humanized antibody fragment having binding specificity to TAG-72.  
     
     
       2. The method according to  claim 1  wherein said effector moiety is a radionuclide, therapeutic enzyme, anti-cancer drug, cytokine, cytotoxin, or anti-proliferative agent. 
     
     
       3. The method according to  claim 1  wherein said humanized antibody is the humanized antibody expressed by a cell deposited as ATCC CRL-12209.